Visceral adiposity in HIV-infected patients is a prevalent and clinically significant clinical problem. Patients with visceral adiposity have a metabolic profile, including insulin resistance, which may predispose to accelerated atherosclerosis. Interventions targeted at improving insulin sensitivity and reducing visceral fat have the potential to favorably modify the risk of cardiovascular disease in this population. Recombinant human growth hormone (rhGH) is a potentially effective treatment for visceral adiposity, but its adverse effects on insulin sensitivity and potential long-term toxicities may limit its usefulness in a patient population with a high underlying prevalence of insulin resistance. Thiazolidinedione drugs, such as rosiglitazone, may have favorable effects on insulin sensitivity and the body composition changes in these patients. The overall objective of this proposal is to determine if co-administration of rhGH and rosiglitazone followed by maintenance therapy with rosiglitazone is safe and a more effective therapy for visceral adiposity than either drug alone. The proposed study is a randomized, double-blind, multicenter clinical trial in which HIV-infected subjects with insulin resistance who meet validated anthropometric criteria for visceral adiposity will be randomized initially in a 2 x 2 factorial design to a 12-week course of rhGH, rosiglitazone, rhGH + rosiglitazone, or double-placebo. At week 12, all subjects will be re-randomized to an additional 24-week course of maintenance therapy with rosiglitazone or placebo (those initially on double-placebo will receive open-label rhGH + rosiglitazone for 12 weeks prior to the second randomization). This clinical trial will address the following specific aims: (1) To determine the individual and interacting effects of rosiglitazone and rhGH on glucose homeostasis; (2) To determine the individual and interacting effects of rosiglitazone and rhGH on body composition; (3) To determine the individual and interacting effects of rosiglitazone and rhGH on markers of cardiovascular risk; and, (4) To determine if longer-term administration of rosiglitazone reduces the re-accumulation of visceral adipose tissue (VAT) after cessation of rhGH therapy. The study will be conducted in the GCRCs of 3 collaborating sites in New York City. Eligible subjects will meet anthropometric criteria for visceral adiposity and have impaired glucose tolerance and/or insulin resistance by the quantitative insulin sensitivity check index (QUICKI). The primary evaluations will be frequently sampled intravenous tolerance tests, oral glucose tolerance tests, and free fatty acid flux by 13C-palmitate dilution for specific aim 1; MRI, dual Xray absorptiometry, indirect calorimetry, food diaries, physical activity records, and deuterated water and sodium bromide dilution for specific aims 2 and 4; and, lipoprotein panels and other markers of cardiovascular risk for specific aim 3. If the results are as predicted, then combination therapy with rhGH and rosiglitazone may prove to be a highly effective treatment for visceral adiposity in HIV-infected patients.